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Genetic regulation of post-translational modification of two distinct proteins. / Landini, Arianna; Trbojević-Akmačić, Irena; Navarro, Pau et al.

In: Nature Communications, Vol. 13, No. 1, 1586, 12.2022.

Research output: Contribution to journal › Article › peer-review

Harvard

Landini, A, Trbojević-Akmačić, I, Navarro, P, Tsepilov, YA, Sharapov, SZ, Vučković, F, Polašek, O, Hayward, C, Petrović, T, Vilaj, M, Aulchenko, YS, Lauc, G, Wilson, JF & Klarić, L 2022, 'Genetic regulation of post-translational modification of two distinct proteins', Nature Communications, vol. 13, no. 1, 1586. https://doi.org/10.1038/s41467-022-29189-5

APA

Landini, A., Trbojević-Akmačić, I., Navarro, P., Tsepilov, Y. A., Sharapov, S. Z., Vučković, F., Polašek, O., Hayward, C., Petrović, T., Vilaj, M., Aulchenko, Y. S., Lauc, G., Wilson, J. F., & Klarić, L. (2022). Genetic regulation of post-translational modification of two distinct proteins. Nature Communications, 13(1), [1586]. https://doi.org/10.1038/s41467-022-29189-5

Vancouver

Landini A, Trbojević-Akmačić I, Navarro P, Tsepilov YA, Sharapov SZ, Vučković F et al. Genetic regulation of post-translational modification of two distinct proteins. Nature Communications. 2022 Dec;13(1):1586. doi: 10.1038/s41467-022-29189-5

Author

Landini, Arianna ; Trbojević-Akmačić, Irena ; Navarro, Pau et al. / Genetic regulation of post-translational modification of two distinct proteins. In: Nature Communications. 2022 ; Vol. 13, No. 1.

BibTeX

@article{a1fcb4e568484820928842f0dcbe9450,
title = "Genetic regulation of post-translational modification of two distinct proteins",
abstract = "Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.",
keywords = "Genome-Wide Association Study, Glycosylation, Immunoglobulin G/metabolism, Protein Processing, Post-Translational, Transferrin/genetics",
author = "Arianna Landini and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Pau Navarro and Tsepilov, {Yakov A.} and Sharapov, {Sodbo Z.} and Frano Vu{\v c}kovi{\'c} and Ozren Pola{\v s}ek and Caroline Hayward and Tea Petrovi{\'c} and Marija Vilaj and Aulchenko, {Yurii S.} and Gordan Lauc and Wilson, {James F.} and Lucija Klari{\'c}",
note = "Funding Information: We thank Dr Nicola Pirastu for sharing his knowledge and experience with Mendelian Randomisation and Jelena ?imunovi? for her technical assistance in the laboratory work. The CROATIA-Korcula study was funded by grants from the MRC (United Kingdom), European Commission Framework 6 project EUROSPAN (contract number LSHG-CT-2006-018947), Croatian Science Foundation (grant 8875) and the Republic of Croatia Ministry of Science, Education and Sports (216-1080315-0302). Genotyping was performed in the Genetics Core of the Clinical Research Facility, University of Edinburgh. We would like to acknowledge all the staff of several institutions in Croatia that supported the CROATIA-Korcula fieldwork, including, but not limited to, the University of Split and Zagreb Medical Schools, Institute for Anthropological Research in Zagreb, and the Croatian Institute for Public Health in Split. The Viking Health Study? Shetland (VIKING) was supported by the MRC Human Genetics Unit quinquennial programme grant ?QTL in Health and Disease?. DNA extractions and genotyping were performed at the Edinburgh Clinical Research Facility, University of Edinburgh. We would like to acknowledge the invaluable contributions of the research nurses in Shetland, the administrative team in Edinburgh and the people of Shetland. Finally, we thank the UK Biobank Resource, approved under application 19655. We acknowledge support from the European Union?s Horizon 2020 research and innovation programme IMforFUTURE (A.L.: H2020-MSCA-ITN/721815); the RCUK Innovation Fellowship from the National Productivity Investment Fund (L.K.: MR/R026408/1); the Russian Science Foundation (RSF) (Y.S.A. and S.Z.S.: 19-15-00115); and the MRC Human Genetics Unit programme grant, ?QTL in Health and Disease? (J.F.W. and C.H.: MC_UU_00007/10). Funding Information: Ministry of Education, Singapore, under its Tier 2 Academic Research Fund (AcRF), Grant/Award Number: MOE2019‐T2‐1‐185; National Natural Science Foundation of China, Grant/Award Number: 71571176 Funding information Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-29189-5",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Genetic regulation of post-translational modification of two distinct proteins

AU - Landini, Arianna

AU - Trbojević-Akmačić, Irena

AU - Navarro, Pau

AU - Tsepilov, Yakov A.

AU - Sharapov, Sodbo Z.

AU - Vučković, Frano

AU - Polašek, Ozren

AU - Hayward, Caroline

AU - Petrović, Tea

AU - Vilaj, Marija

AU - Aulchenko, Yurii S.

AU - Lauc, Gordan

AU - Wilson, James F.

AU - Klarić, Lucija

N1 - Funding Information: We thank Dr Nicola Pirastu for sharing his knowledge and experience with Mendelian Randomisation and Jelena ?imunovi? for her technical assistance in the laboratory work. The CROATIA-Korcula study was funded by grants from the MRC (United Kingdom), European Commission Framework 6 project EUROSPAN (contract number LSHG-CT-2006-018947), Croatian Science Foundation (grant 8875) and the Republic of Croatia Ministry of Science, Education and Sports (216-1080315-0302). Genotyping was performed in the Genetics Core of the Clinical Research Facility, University of Edinburgh. We would like to acknowledge all the staff of several institutions in Croatia that supported the CROATIA-Korcula fieldwork, including, but not limited to, the University of Split and Zagreb Medical Schools, Institute for Anthropological Research in Zagreb, and the Croatian Institute for Public Health in Split. The Viking Health Study? Shetland (VIKING) was supported by the MRC Human Genetics Unit quinquennial programme grant ?QTL in Health and Disease?. DNA extractions and genotyping were performed at the Edinburgh Clinical Research Facility, University of Edinburgh. We would like to acknowledge the invaluable contributions of the research nurses in Shetland, the administrative team in Edinburgh and the people of Shetland. Finally, we thank the UK Biobank Resource, approved under application 19655. We acknowledge support from the European Union?s Horizon 2020 research and innovation programme IMforFUTURE (A.L.: H2020-MSCA-ITN/721815); the RCUK Innovation Fellowship from the National Productivity Investment Fund (L.K.: MR/R026408/1); the Russian Science Foundation (RSF) (Y.S.A. and S.Z.S.: 19-15-00115); and the MRC Human Genetics Unit programme grant, ?QTL in Health and Disease? (J.F.W. and C.H.: MC_UU_00007/10). Funding Information: Ministry of Education, Singapore, under its Tier 2 Academic Research Fund (AcRF), Grant/Award Number: MOE2019‐T2‐1‐185; National Natural Science Foundation of China, Grant/Award Number: 71571176 Funding information Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.

AB - Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.

KW - Genome-Wide Association Study

KW - Glycosylation

KW - Immunoglobulin G/metabolism

KW - Protein Processing, Post-Translational

KW - Transferrin/genetics

UR - http://www.scopus.com/inward/record.url?scp=85127028681&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-29189-5

DO - 10.1038/s41467-022-29189-5

M3 - Article

C2 - 35332118

AN - SCOPUS:85127028681

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1586

ER -

ID: 35780037